International Aid Inc

HIV VACCINE AND BIOMEDICAL PREVENTION RESEARCH PROJECT OBJECTIVES 1 AND 2 - ADVANCE

TO PROVIDE INCREMENTAL FUNDING IN THE AMOUNT OF $28 710 000

MISC OHA COOPERATIVE AGREEMENTS

PUSHING THE ENVELOPE: OPTIMIZING VACCINE DISPLAY OF FLEXIBLY LINKED HIV ENV TRIMER IMMUNOGENS

INTERPLAY OF B CELLS AND HIV LEADING TO BROAD NEUTRALIZING ANTIBODY RESPONSES

ADVANCING A PROMISING TUBERCULOSIS VACCINE CANDIDATE: MTBVAC

USING VSV VECTORS TO DISPLAY AND EVOLVE NOVEL HIV ENVELOPE IMMUNOGENS

DEVELOPMENT OF NOVEL MRNA VACCINES AGAINST MYCOBACTERIUM TUBERCULOSIS - PROJECT SUMMARY/ABSTRACT TUBERCULOSIS REMAINS ONE OF THE TOP TEN LEADING CAUSES OF DEATH WORLDWIDE (1). BASED ON THE MOST CURRENT INFORMATION FROM WHO 2020 REPORT, IN 2019 AN ESTIMATED 1.4 MILLION PEOPLE DIED FROM TB AND APPROXIMATELY 10,000,000 FELL ILL (2). THE COVID-19 PANDEMIC HAS LED TO MASSIVE DECREASES IN TB CASE IDENTIFICATION AND STOP TB ESTIMATES AN ADDITIONAL 1.4 MILLION TB DEATHS WILL BE REGISTERED OVER THE NEXT 4 YEARS (3, 4). THIS, TOGETHER WITH THE GROWING THREAT OF DRUG-RESISTANT TB AND THE CO-EPIDEMICS OF TB WITH HIV AND DIABETES MAKES ENDING THE TB EPIDEMIC MORE CRUCIAL THAN EVER BEFORE. A VACCINE THAT PREVENTS ADOLESCENTS AND ADULTS FROM ACQUIRING, DEVELOPING, AND TRANSMITTING TB WOULD BE THE SINGLE MOST COST-EFFECTIVE TOOL IN ENDING THE TB EPIDEMIC (5). THE TUBERCULOSIS VACCINE INITIATIVE (TBVI) AND TREATMENT ACTION GROUP (TAG) TB VACCINE PIPELINES REPORT TWELVE SUBUNIT VACCINES INCLUDING RECOMBINANT PROTEIN/ADJUVANT AND VIRAL VECTOR VACCINES SPANNING FROM PRECLINICAL THROUGH PHASE 3 DEVELOPMENT (6, 7). OF THESE, NINE INCLUDE AG85 (AG85A OR B) AND SIX INCLUDE ESAT6. THE HIGHLY LIMITED ANTIGENIC AND IMMUNOLOGICAL DIVERSITY PRESENT IN THE PIPELINE IS A SIGNIFICANT GAP IN EFFORTS TO DEVELOP A NOVEL, EFFECTIVE VACCINE. THE PROPOSED RESEARCH IS INTENDED TO BRING NEEDED ANTIGENIC AND PLATFORM DIVERSITY TO THE PRE-CLINICAL TB VACCINE PIPELINE USING MODERNA’S CUTTING-EDGE MRNA VACCINE TECHNOLOGY AND EXPERTISE. WITHIN THE R61 PHASE OF THIS PROGRAM, WE WILL FIRST OPTIMIZE MYCOBACTERIAL ANTIGEN SEQUENCES FOR EXPRESSION IN MAMMALIAN CELLS USING MODERNA’S PROPRIETARY LEARNINGS AND ALGORITHMS. THESE PRINCIPLES WILL BE APPLIED TO THE DEVELOPMENT OF THREE CANDIDATE MRNA VACCINES, INCLUDING 1) AN ANTIGEN CASSETTE PREVIOUSLY SHOWN TO INDUCE PROTECTION IN ANIMAL MODELS WHEN DELIVERED AS A PROTEIN PLUS ADJUVANT, 2) A NEW ANTIGEN CASSETTE INCLUDING NOVEL ANTIGENS, AND 3) THE M72 ANTIGEN SHOWN TO INDUCE PROTECTION IN HUMANS WHEN DELIVERED AS RECOMBINANT PROTEIN WITH THE AS01E ADJUVANT. WE WILL THEN USE DATA FROM MURINE IMMUNOGENICITY AND PROTECTION STUDIES TO SELECT THE TWO BEST CANDIDATES FOR ADVANCEMENT INTO THE R33 PHASE. WITHIN THE R33 PHASE, WE WILL USE THE GUINEA PIG CHALLENGE MODEL TO DOWNSELECT TO A FINAL LEAD CANDIDATE FOR FURTHER ADVANCEMENT. ONCE A FINAL LEAD CANDIDATE IS SELECTED, ADDITIONAL STUDIES WILL BE CONDUCTED TO FURTHER CHARACTERIZE THE CANDIDATE, INCLUDING PROTECTION IN GENETICALLY DIVERSE MICE AND AN IMMUNOGENICITY STUDY IN NONHUMAN PRIMATES TO OPTIMIZE THE VACCINATION REGIMEN FOR CLINICAL USE. BY THE END OF THIS PROGRAM, WE WILL HAVE A NOVEL LEAD VACCINE CANDIDATE READY FOR ADVANCEMENT INTO IND- ENABLING STUDIES AND EARLY DEVELOPMENT AS A VACCINE TO PREVENT TB DISEASE IN ADULTS AND ADOLESCENTS.

DEVELOPMENT OF NOVEL MRNA VACCINES AGAINST MYCOBACTERIUM TUBERCULOSIS - PROJECT SUMMARY/ABSTRACT TUBERCULOSIS REMAINS ONE OF THE TOP TEN LEADING CAUSES OF DEATH WORLDWIDE (1). BASED ON THE MOST CURRENT INFORMATION FROM WHO 2020 REPORT, IN 2019 AN ESTIMATED 1.4 MILLION PEOPLE DIED FROM TB AND APPROXIMATELY 10,000,000 FELL ILL (2). THE COVID-19 PANDEMIC HAS LED TO MASSIVE DECREASES IN TB CASE IDENTIFICATION AND STOP TB ESTIMATES AN ADDITIONAL 1.4 MILLION TB DEATHS WILL BE REGISTERED OVER THE NEXT 4 YEARS (3, 4). THIS, TOGETHER WITH THE GROWING THREAT OF DRUG-RESISTANT TB AND THE CO-EPIDEMICS OF TB WITH HIV AND DIABETES MAKES ENDING THE TB EPIDEMIC MORE CRUCIAL THAN EVER BEFORE. A VACCINE THAT PREVENTS ADOLESCENTS AND ADULTS FROM ACQUIRING, DEVELOPING, AND TRANSMITTING TB WOULD BE THE SINGLE MOST COST-EFFECTIVE TOOL IN ENDING THE TB EPIDEMIC (5). THE TUBERCULOSIS VACCINE INITIATIVE (TBVI) AND TREATMENT ACTION GROUP (TAG) TB VACCINE PIPELINES REPORT TWELVE SUBUNIT VACCINES INCLUDING RECOMBINANT PROTEIN/ADJUVANT AND VIRAL VECTOR VACCINES SPANNING FROM PRECLINICAL THROUGH PHASE 3 DEVELOPMENT (6, 7). OF THESE, NINE INCLUDE AG85 (AG85A OR B) AND SIX INCLUDE ESAT6. THE HIGHLY LIMITED ANTIGENIC AND IMMUNOLOGICAL DIVERSITY PRESENT IN THE PIPELINE IS A SIGNIFICANT GAP IN EFFORTS TO DEVELOP A NOVEL, EFFECTIVE VACCINE. THE PROPOSED RESEARCH IS INTENDED TO BRING NEEDED ANTIGENIC AND PLATFORM DIVERSITY TO THE PRE-CLINICAL TB VACCINE PIPELINE USING MODERNA’S CUTTING-EDGE MRNA VACCINE TECHNOLOGY AND EXPERTISE. WITHIN THE R61 PHASE OF THIS PROGRAM, WE WILL FIRST OPTIMIZE MYCOBACTERIAL ANTIGEN SEQUENCES FOR EXPRESSION IN MAMMALIAN CELLS USING MODERNA’S PROPRIETARY LEARNINGS AND ALGORITHMS. THESE PRINCIPLES WILL BE APPLIED TO THE DEVELOPMENT OF THREE CANDIDATE MRNA VACCINES, INCLUDING 1) AN ANTIGEN CASSETTE PREVIOUSLY SHOWN TO INDUCE PROTECTION IN ANIMAL MODELS WHEN DELIVERED AS A PROTEIN PLUS ADJUVANT, 2) A NEW ANTIGEN CASSETTE INCLUDING NOVEL ANTIGENS, AND 3) THE M72 ANTIGEN SHOWN TO INDUCE PROTECTION IN HUMANS WHEN DELIVERED AS RECOMBINANT PROTEIN WITH THE AS01E ADJUVANT. WE WILL THEN USE DATA FROM MURINE IMMUNOGENICITY AND PROTECTION STUDIES TO SELECT THE TWO BEST CANDIDATES FOR ADVANCEMENT INTO THE R33 PHASE. WITHIN THE R33 PHASE, WE WILL USE THE GUINEA PIG CHALLENGE MODEL TO DOWNSELECT TO A FINAL LEAD CANDIDATE FOR FURTHER ADVANCEMENT. ONCE A FINAL LEAD CANDIDATE IS SELECTED, ADDITIONAL STUDIES WILL BE CONDUCTED TO FURTHER CHARACTERIZE THE CANDIDATE, INCLUDING PROTECTION IN GENETICALLY DIVERSE MICE AND AN IMMUNOGENICITY STUDY IN NONHUMAN PRIMATES TO OPTIMIZE THE VACCINATION REGIMEN FOR CLINICAL USE. BY THE END OF THIS PROGRAM, WE WILL HAVE A NOVEL LEAD VACCINE CANDIDATE READY FOR ADVANCEMENT INTO IND- ENABLING STUDIES AND EARLY DEVELOPMENT AS A VACCINE TO PREVENT TB DISEASE IN ADULTS AND ADOLESCENTS.

MTBVAC PHASE 1B/2A RANDOMIZED, DOUBLE-BLIND, ACTIVE-CONTROLLED, SAFETY, IMMUNOGENICITY, AND DOSE-ESCALATION STUDY IN ADULTS WITH AND WITHOUT LATENT TUBERCULOSIS INFECTION IN SOUTH AFRICA

PUBLIC HEALTH CONFERENCE SUPORT

CHILD SURVIVAL AND HEALTH GRANT PROGRAM COOPERATIVE AGREEMENT WITH INTERNATIONAL AID. THE PURPOSE OF MODIFICATION #2 WAS INCORPORATE MAJOR CHANGES T

NATIONAL CENTER FOR HIV, VIRAL HEPATITIS, SEXUALLY TRANSMITTED DISEASE AND TUBERC

HOMELESS ASSISTANCE

SCREENING FOR HIV-1 ENVELOPE MIMETICS FROM SMALL MOLECULE LIBRARIES

CONTINUUM OF CARE PROGRAM

CONTINUUM OF CARE PROGRAM

HOMELESS ASSISTANCE

HOMELESS ASSISTANCE

CONTINUUM OF CARE PROGRAM

6TH GLOBAL FORUM ON TB VACCINES - PROJECT SUMMARY/ABSTRACT THE GLOBAL FORUM ON TB VACCINES (GLOBAL FORUM) IS THE WORLD’S LARGEST GATHERING OF STAKEHOLDERS STRIVING TO DEVELOP NEW VACCINES TO PREVENT TUBERCULOSIS (TB). IN 2018, TB KILLED AN ESTIMATED 1.5 MILLION PEOPLE, MORE THAN ANY OTHER SINGLE INFECTIOUS DISEASE AGENT, AND 10 MILLION BECOME SICK WITH THE DISEASE (1). THE UNITED NATIONS’ SUSTAINABLE DEVELOPMENT GOALS (SDGS), THE WORLD HEALTH ORGANIZATION’S (WHO) END TB STRATEGY, AND THE STOP TB PARTNERSHIP’S GLOBAL PLAN TO END TB 2018-2022 RECOGNIZE THAT NEW VACCINES WILL BE IMPERATIVE TO REACHING GLOBAL TARGETS TO ELIMINATE TB; AND WORLD LEADERS COMMITTED TO SUPPORTING RESEARCH AND DEVELOPMENT (R&D) OF NEW TOOLS TO END TB IN THE POLITICAL DECLARATION FROM THE UNITED NATIONS HIGH-LEVEL MEETING ON TB IN 2018. THE GLOBAL FORUM PROVIDES A UNIQUE OPPORTUNITY FOR THE TB VACCINE R&D COMMUNITY TO COME TOGETHER TO REVIEW THE STATE OF THE FIELD, SHARE THE LATEST RESEARCH AND FINDINGS, AND IDENTIFY NEW AND INNOVATIVE APPROACHES TO TB VACCINE R&D. PROGRAM TOPICS RANGE FROM BASIC RESEARCH TO CLINICAL TRIALS, LICENSURE, ACCESS, AND ADVOCACY. THE 6TH GLOBAL FORUM ON TB VACCINES IS PLANNED TO TAKE PLACE IN TOULOUSE, FRANCE FROM APRIL 20 – 22, 2021. THE EUROPEAN REGION HAS LONG BEEN AT THE FOREFRONT OF TB VACCINE RESEARCH AND INNOVATION; AND FRANCE’S LEADERSHIP AND COMMITMENT TO GLOBAL HEALTH, ITS EXCELLENCE IN TUBERCULOSIS (TB) VACCINE RESEARCH, AND TOULOUSE’S REPUTATION AS A KNOWLEDGE HUB AND CENTER FOR INNOVATION MAKE THIS AN EXCITING AND APPROPRIATE VENUE FOR THE 6TH GLOBAL FORUM. AS WITH PAST GLOBAL FORUMS, THE 6TH GLOBAL FORUM WILL PROVIDE A PLATFORM FOR SCIENTIFIC EXCHANGE AND GLOBAL DISCOURSE ON THE PATH FORWARD FOR TB VACCINE R&D, AS WELL AS OPPORTUNITIES TO IDENTIFY POTENTIAL PARTNERS AND COLLABORATORS. THE ORGANIZERS WILL SEEK WAYS TO ENHANCE NETWORKING OPPORTUNITIES, PROMOTE INTERACTIONS AMONGST PARTICIPANTS, AND BRING TOGETHER PARTICIPANTS WITH COMMON INTERESTS. ADDITIONALLY, THE GLOBAL FORUM ENCOURAGES AND SUPPORTS EARLY CAREER RESEARCHERS IN SHARING THEIR RESEARCH AND OFFERS MULTIPLE OPPORTUNITIES TO LEARN FROM AND ENGAGE WITH EXPERTS IN THE FIELD. IAVI IS REQUESTING FUNDING FROM THE NIH TO SUPPORT TRAVEL FOR EARLY-CAREER RESEARCHERS AND PARTICIPANTS FROM TB ENDEMIC COUNTRIES WHO WOULD NOT OTHERWISE HAVE THE RESOURCES TO ATTEND, PRESENT THEIR RESEARCH, OR PARTICIPATE IN THE DISCUSSIONS THAT TAKE PLACE AT THE 6TH GLOBAL FORUM. THE 6TH GLOBAL FORUM WILL FOLLOW ON THE 5TH GLOBAL FORUM IN NEW DELHI, INDIA (2018); 4TH GLOBAL FORUM IN SHANGHAI, CHINA (APRIL 2015); 3RD GLOBAL FORUM IN CAPE TOWN, SOUTH AFRICA (MARCH 2013); AND 2ND GLOBAL FORUM IN TALLINN, ESTONIA (SEPTEMBER 2010). THE FIRST GLOBAL FORUM ON TB VACCINES WAS ORGANIZED BY THE WHO AND TOOK PLACE IN GENEVA IN 2001.